Eighty percent of the world's human immunodeficiency virus (HIV) infections are in Africa, where heterosexual contact is the predominant mode of transmission. In Zambia, the prevalence of HIV in urban adults now exceeds 30%. Most new infections occur in cohabiting couples, 20% of whom have discordant HIV serology results. Our previous research has shown that voluntary HIV testing and counseling (VTC) provokes reductions of >50% in seroconversion rates among discordant couples, but transmission remains relatively frequent at 7-9%/year. The correlates of number of unprotected contacts in discordant couples have been described, but much remains to be learned about the determinants of transmission risk per unprotected contact. Ulcerative and non-ulcerative sexually transmitted diseases (STD) have been implicated in this vein, but these diseases are uncommon in married African couples. Only 5% of seroconvertors in our previous studies of Rwandan women had a genital ulcer or gonorrhea. Vaginal discharge was far more common and was associated with an increased risk of seroconversion in multivariate analyses. Genital pathogens usually considered banal, including candida and bacterial vaginosis, may have a significant impact on spread of HIV simply because of their high prevalence. Discordant heterosexual couples are an ideal group in which to address the following questions: (a) Why does HIV transmission occur after only a few unprotected contacts in some discordant couples while in others, transmission does not occur despite hundreds of exposures? (b) Is the risk of female to male transmission related to HIV shedding in cervicovaginal fluids? (c) Can women be grouped into shedders and non- shedders, or is HIV shedding random? (d) Is shedding more common in the presence of STD or vaginal discharge? (e) Can the contribution of STD and other genital conditions to heterosexual HIV transmission be better quantified at the individual (relative risk) and population (attributable risk) level? A research team with 8 years experience in Rwanda has relocated to Lusaka, Zambia. A voluntary HIV testing center for couples has been established and over 2400 couples have sought testing. We propose a 4 year follow-up of 600 discordant couples. Based on our previous experience, we expect 250 seroconversions, including 125 female to male and 125 male to female transmissions. Three monthly examinations will include routine screening for genital pathogens, clinical and laboratory staging of HIV disease, and banking of serum and cervicovaginal fluids. A nested case-control design will be used to compare HIV shedding over time in women who transmit to their partners and women who don't.